摘要
背景:阿尔茨海默病(AD)的特点是β淀粉样蛋白的积累,神经原纤维缠结tau蛋白的磷酸化,神经炎症,突触变性和最终的神经元细胞的损失。目前的治疗方法能是AD患者临时缓解症状。这些药物包括改善胆碱能神经支配的胆碱酯酶抑制剂,如卡巴拉汀,盐酸多奈哌齐与galatamine。此外,拮抗剂美金刚胺-N-甲基-D-天门冬氨酸,可减少兴奋性中毒而用于治疗中度至重度AD。研究表明兴奋增加和抑制减少导致AD患者异常兴奋性神经元的活动和认知功能障碍。 方法:我们通过数据库对与AD患者神经活动有关的文献进行检索。基于与人类和啮齿类动物模型中兴奋增加或神经网络抑制相关性确定纳入/排除标准。最终的标准定为α-黑素细胞刺激素(αMSH)作为治疗阿尔茨海默病的潜在药物。 结果:我们最终确定了156个其中同行评审刊符合我们的标准。AD和老化都表现出认知障碍和gabaerigc神经元抑制损失。α-黑素细胞刺激素是一种神经肽,它在AD患者的大脑和脑脊液是下调的。α-MSH具有多种功能的中枢神经系统包括神经保护作用和抗炎作用。在小鼠模型中,αMSH治疗促进海马GABA能中间神经元的生存,改善空间记忆以及焦虑的症状。αMSH治疗能保护GABA能中间神经元亚群表达生长抑素。生长抑素与海马依赖的认知功能有关。生长抑素表达神经元也能保持兴奋抑制平衡中发挥重要作用。αMSH保护GABA能中间神经,预防生长抑素亚群的丢失,改善认知功能。 结论:αMSH是一种新型的治疗AD的方法,但其治疗AD患者的潜力有待进一步研究。
关键词: 阿尔茨海默病,α-促黑素细胞激素,神经保护,生长抑素
Current Alzheimer Research
Title:α-Melanocyte Stimulating Hormone as a Potential Therapy for Alzheimer's Disease
Volume: 14 Issue: 1
Author(s): Keran Ma and JoAnne McLaurin
Affiliation:
关键词: 阿尔茨海默病,α-促黑素细胞激素,神经保护,生长抑素
摘要: Background: Alzheimer's disease (AD) is characterized by accumulation and aggregation of beta-amyloid peptide, neurofibrillary tangles of hyperphosphorylated tau, neuroinflammation, synaptic degeneration and eventual neuronal cell loss. Current treatment options for AD provide temporary symptomatic relief in a subset of patients. These drugs include cholinesterase inhibitors that improve cholinergic innervation such as rivastigmine, donepezil and galatamine. In addition, memantine, a Nmethyl- D-aspartate antagonist, is used to treat moderate to severe AD by reducing excitotoxicity. It has been proposed that increased excitation and decreased inhibition lead to aberrant excitatory neuronal activity and cognitive deficits in AD.
Methods: We undertook a search of the literature using bibliographic databases to identify publications that were related to neuronal activity in Alzheimer's disease. We further delineated the publications to determine inclusion/exclusion criteria based on relevance to increased excitation or decreased inhibition of neuronal networks in both human patients and rodent models. The final criteria related to the potential use of α-Melanocyte stimulating hormone (α-MSH) as a potential treatment strategy for Alzheimer's disease. These data were utilized to obtain the content of this review. Results: We identified 156 peer-reviewed publications that met our criteria and describe the findings here. Rodent models of AD and ageing both exhibit cognitive deficits and loss of inhibitory GABAerigc interneurons. α-Melanocyte stimulating hormone is a neuropeptide that is down-regulated in the brain and cerebrospinal fluid of AD patients. α-MSH has many functions in the central nervous system including neuroprotective and anti-inflammatory effects that target multiple aspects of the AD pathology. α-MSH treatment promoted the survival of GABAergic interneurons in the hippocampus and improved spatial memory as well as alterations in anxiety in a mouse model of AD. The somatostatin expressing subpopulation of GABAergic interneurons are particularly preserved by α-MSH treatment. Somatostatin has been implicated in hippocampal-dependent cognitive tasks. Somatostatin-expressing interneurons have also been shown to play an important role in maintaining excitatory-inhibitory balance. α-MSH preserved GABAergic interneurons and by preventing the loss of the somatostatin subpopulation, it improved cognitive function. Conclusion: α-MSH is a novel candidate for the treatment of AD but its therapeutic potential in AD patients remains to be investigated.Export Options
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Cite this article as:
Keran Ma and JoAnne McLaurin , α-Melanocyte Stimulating Hormone as a Potential Therapy for Alzheimer's Disease, Current Alzheimer Research 2017; 14 (1) . https://dx.doi.org/10.2174/1567205013666160819130641
DOI https://dx.doi.org/10.2174/1567205013666160819130641 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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